This study aims to conduct a functional genomic analysis of variation in the efficacy of innate immune defense in Drosophila melanogaster, to enhance the understanding of the genetic bases of innate immunity. Insect innate immunity is an excellent model for vertebrate preadaptive immunity. The research conducted in this study will accomplish two key health-related goals: the identification of novel antimicrobial proteins of antibiotic-design potential, and importantly, the identification of host genes responsible for variation among individuals in immune defense as potential therapeutic targets. The specific aims of the study are: First, to quantify the expression kinetics of immune defense genes after infection with a natural pathogen in Drosophila strains that vary in their ability to defend against infection. Second, to apply DNA microarray analysis to these strains, in order to identify novel defense-gene regulatory targets, quantify variation in the kinetics of genome-wide expression during infection, and to identify sequence divergence contributing to known immunity quantitative trait loci.